Cellular Allorecognition of HLA-B27: Clonal Heterogeneity and Identification of Immunodominant Sites
Eighteen CD3+CD4−CD8+ HLA-B27 allospecific cytolytic T-lymphocyte (CTL) clones were isolated by limiting dilution of HLA-B27-negative responder cells stimulated with HLA-B27.1-positive lymphoblastoid cells. The specificity and avidity of these clones was determined from panel analyses, cold-target competition studies, inhibition with anti-HLA monoclonal antibodies, and blocking studies with anti-CD3 and anti-CD8 antibodies. Target HLA antigens of known structure, including all the structurally characterized HLA-B27 subtypes, were used in order to examine how the polymorphism at particular amino acid sequence positions modulates the fine specificity of each CTL clone. As shown in Table 1, seven reaction patterns were distinguished on the basis of their differential reactivaties with the various B27 subtypes and of crossreactions with HLA-B40* or HLA-DR2. The crossreactivity of CTL clones 23, 27, and 47 with B27.1 and HLA-DR2 has been analyzed in detail elsewhere (1). Otherwise, these reaction patterns were characterized by: lack of recognition of those B27 subtypes (B27.3 and B27.4) with a change at position 152; and altered reactivity towards a variant with changes in the segment 77–81 (B27.2) and sometimes with those differing at residues 74–81 (B27f) or at position 59 (B27d).